Part II: Retinol Metabolism Cont’d; Retinol Degradation and Strength; Combination Use of (Hydroxy) Acids and Retinol

FAQs about Retinol

In Part I, we discussed the main pathway of retinol metabolism and learned that in order to allow the skin to OPTIMALLY convert retinol into retinaldehyde, and then into tretinoin, a retinol product should have a pH value of between ~5.0-6.0.

So the obvious question that is asked most often is, “Can I use retinol and hydroxy acid products together?”

Based on research and my interpretation of the literature, they should not be used together. This stance has drawn particular criticism HERE from advocates of Paula Begoun, the creator of Paula’s Choice, who attempted to answer this question HERE. Please note that I too, am an advocate of Paula Begoun and her products. I just don’t always agree with some of her rationalizations and interpretations of scientific data.

Now, before you start drawing conclusions, let us walk through and analyze her post. In critiquing it, perhaps we can come up with an independent and more realized assessment. So that you guys (the readers) don’t have to keep skipping back and forth between pages/tabs, I will simply copy and paste the entire article here and address it section by section.

*Please note that the studies Paula referenced will be denoted as [#X], with “X” being a numerical value, and along with the rest of her post, are italicized and bolded. The studies that I reference will be denoted as [(X)] and are not italicized and not bolded. In addition, there will be parentheses around the number or “X”.

Fan FAQs: Retinol, pH and Daytime Use?

Q: “My dermatologist says that it is well-known that retinol increases your sensitivity to the sun, and that I shouldn’t use it during the daytime because sunlight deactivates it. How do you know if I can use my PC retinol during the day?

Is it true that over-the-counter retinol is 20 times weaker than Retin-A and doesn’t work as well? My derm also says that retinol needs a certain pH to work and it shouldn’t be applied with other acidic ingredients. I am so confused!”

A: All retinoids, particularly prescription retinoids like tretinoin, increase skin’s sensitivity to the sun to an extent. We know that tretinoin (the active ingredient in Retin-A and Renova) is deactivated by sunlight; it becomes unstable with exposure to UV rays. Cosmetic, non-prescription retinol is not as unstable, and research has shown when applying a broad-spectrum sunscreen over cosmetic retinol, there is no loss of effectiveness. This doesn’t necessarily mean a day at the beach, but certainly what hasn’t been shown in research is that retinol is unstable when SPF measures are taken.

Paula uses studies #2 and #3 to substantiate this claim. Study #3 will be ignored because one, it hasn’t been peer-reviewed or published in any known journal (it can’t even be found on PubMed); two, the UV blocker discussed isn’t traditionally used (Ethylhexyl Methoxycrylene) or available in sunscreens; and three, the author of the article has a conflict of interest, being that his organization is affiliated with the supplier of the UV blocker discussed.

Now study #2, which can be found HERE, combines retinol with a formulation of avobenzone (UVA sunscreen), octinoxate (UVB sunscreen), and the antioxidant vitamins C and E. The study tested this formulation (4 experimental groups + 1 control group) under varying degrees of light and air, and measurements of retinol stability were taken at 0.5, 1.0, 2.0, and 4.0 hours. At the end of 4.0 hours, when compared to the control group, retinol stability was at 91.3% (UV & nitrogen gas (N2)), 91.5% (UV & air), 96.9% (N2), and 99.2% (air). Please note that the rates of degradation weren’t strictly linear.

At first glance <10% of retinol degradation after 4.0 hours of UV and air exposure, is quite good. However, there are a few things that need to be kept in mind:

>>> We know that, to any sunscreen formulation, the inclusion of both vitamins C and E, can massively boost the level of UV protection (1), up to 4-fold. Numerous other studies support this concept. Study #2 didn’t test retinol stability with only the protection of sunscreen (avobenzone and octinoxate), which most likely would have yielded significantly different results. And the study didn’t test if there were interactions between the hydroquinone and retinol contents, not to mention the effects of the “moisturizers,” as the latter can have a large effect on UV protection. Basically, because this study wasn’t vehicle-controlled, it has no real value. However, I will still address the rest of this study.

>>> In real life situations, this rate of 10% degradation over 4.0 hours needs to be perceived contextually, meaning that the rate of degradation needs to be calculated from a point of reference, which of course, is how much retinol has already degraded. When we purchase a retinol product, we don’t use all of it up immediately. So despite efforts to stabilize the retinol via formulary and packaging choices, the retinol in any product will degrade over time. So in a month, perhaps 10% of the retinol INSIDE the bottle has already decayed, and with exposure to UV light and air, will degrade even further. Why take that risk? Just use retinol at night-time. As you can see from the study, group 3 (exposed to air), only had a degradation of 0.8% after 4.0 hours. That’s more than 10x less than that which occurs with the addition of UV light!

>>> Overall, while this claim certainly has value and merit (I have read other articles that support this), it’s just better and smarter to use retinol at night time. At the right concentration and formulation, using retinol every night will be sufficient and potent enough for most people. In fact, it may even be TOO potent. There are no benefits (only potential drawbacks) to using retinol during the day.

In terms of retinol’s strength vs. that of prescription retinoids, we’ve seen various figures as to how they compare. However, the “20 times weaker” number comes up most often—but the question is whether that is relevant to you, as all this means is that cosmetic retinol takes longer to show the same results as tretinoin, which is why tretinoin requires a prescription.

The often cited “20 times” reference refers to a 1988 study on mice, of which references a 1987 study on mice, which really isn’t that impressive when you consider the depth of research since showing the anti-aging benefit of cosmetic retinol in skin care, especially when combined with a well-formulated skin care routine.

Paula doesn’t actually cite the 1987/1988 studies, but I can tell you that “20 times weaker” is quite an accurate measurement of the strength of retinol vs that of tretinoin.

>>> Like I’ve said many times in the past, keep in mind that the word “strength” only refers to how much tretinoin accumulates in the skin. Therefore, if you apply 1 unit of tretinoin, 1 unit of tretinoin will be in contact with the skin. However, if you apply 1 unit of retinol, only about 1/20th of a unit of tretinoin will come into existence due to the average rate of conversion. It doesn’t necessarily mean that you need 20 units of retinol to achieve the same visible effects that 1 unit of tretinoin can do, as several studies have demonstrated that low levels of tretinoin can have similar effects on the skin as higher levels (2). It just varies from person to person.

>>> Also, Paula’s assertion that it just takes retinol longer to achieve the same results as tretinoin (basically that it takes something like 20 days of retinol use to achieve the safe effects as 1 day of tretinoin use), is untrue. Why do you think there are varying degrees of tretinoin available at the pharmacy? Because different people and disorders respond to different strengths of tretinoin. In terms of retinol, different people can have different physiological capabilities to convert/metabolize it to tretinoin. Not to mention, the existence of varying and unregulated degrees of efficacy when it comes to retinol products, which have different delivery systems, stabilizers (if any), etc… To make a blanket statement that retinol will do the same thing as tretinoin, with just more time, is lazy, inaccurate, and unsupported by evidence. This topic will be explored further in Part III, which will explain why retinol can never replace tretinoin.

>>> Now, to show evidence of my own, several studies including this one (3) have established that the skin converts retinol to tretinoin at a rate of about 5%, on average. The cited study measured the rates at which expression of the enzyme, type I epidermal transglutaminase (TET-1), were reduced when retinol or tretinoin was applied to the skin. (Reduction of TET-1 expression is a well-known indicator of tretinoin activity). The study discovered that approximately half-maximal (EC50) reduction was observed at 10 nM retinol and 1 nM of tretinoin, indicating that tretinoin is about 10 times more potent than retinol. Before you tell me that “10” is not the same as “20,” keep this in mind. The study also showed that most of the retinol converted to retinyl esters, and that as retinol concentration increased, only marginally more tretinoin appeared in the skin, indicating the same concept I stated in Part I: that the metabolism of retinol to tretinoin is strictly regulated by the skin. But because tretinoin cannot be reduced back to retinaldehyde, how much tretinoin is applied to the skin, is what the skin has to deal with. Therefore, because it was demonstrated that 10 units of retinol was required to achieve the same results seen with 1 unit of tretinoin for HALF-maximal response, FULL “maximal” response would be twice that number. Hence, 10 x 2 = 20. Keep in mind that this was done to test the capacity of response. It was not referring to the threshold of response, meaning that there is no “baseline” concentration that can be applied to everyone.

>>> Therefore, the modified conclusion that: tretinoin is UP TO and ABOUT 20 times stronger than retinol, is quite true!

The upside of retinol versus prescription tretinoin? There is a significantly reduced likelihood your skin will experience negative side effects (redness, flaking, sensitivity) from retinol than from tretinoin. So if you’re willing to be patient, you’ll find results from retinol will, over time, equate to those from prescription tretinoin.

Paula has no citation for this claim, but fortunately it’s true. Retinol is comparatively much less irritating than tretinoin (4). However, like I discussed above, retinol won’t necessarily have the same effects as tretinoin when used over time.

We have not seen any research indicating that retinol needs a certain pH to work—this is one of the strangest misunderstandings in skin care recently. The research cited when you hear the claim of retinol needing a pH of 5.5-6 is from 1990, and this demonstrates why it is important to understand the study before using it to back your claims. The 1990 research discussed the formation of skin cells in response to all-trans retinol (tretinoin), and no surprise, your skin’s cell production is optimal at the skin’s natural pH, which is 5.5-6. Surprisingly, the study’s authors did not use cosmetic retinol (all-trans retinol is the prescription version) and in the end, the pH discussion is all about the optimal level for skin, not retinol!

One more point: retinol is naturally acidic (the prescription form is also known as retinoic acid) which is why some people find they’re sensitive to it.

Paula says that study #1, which can be found HERE, is the basis for the (in her opinion) false claim that retinol needs a certain pH in order to function. She is correct in the sense that retinol does NOT need a certain pH to function. But as I stated in Part I, she is incorrect in the sense that a retinol product doesn’t need a certain pH range in order to allow the skin to OPTIMALLY CONVERT retinol into tretinoin. But let’s get into the study and point out the fallacies made.

>>> Paula discusses study #1, as if it were correctly used to substantiate the fact that retinol products need a pH of 5.5-6.0. She goes on to explain why that study doesn’t apply. But the problem is that, study #1 shouldn’t even be used to explain this idea! As I explained in Part I, the 5.5-6.0 pH range is the optimal range necessary for the enzyme, acyl CoA:retinol acyltransferase (ARAT), to optimally convert retinol to retinyl esters, which is going in the complete OPPOSITE direction on the retinol metabolic pathway! The enzymes responsible for the conversion of retinol to tretinoin are completely different, and have different (higher and more basic) optimal pH ranges! Once again, see Part Ifor more information. By not addressing this issue, Paula shows a serious lack in judgment.

>>> Not to mention that she also equates all-trans-retinol to tretinoin, which are definitely not the same. The “all-trans” prefix only denotes directional configuration, not compound identification. Jack, one of my readers, claimed in the silicone entrapment discussion, that as a “professional” talking to laypersons, Paula was flexibly interchanging scientific terms to not confuse us. But she supposedly knows the difference between the two. Well, I don’t know what she THOUGHT, but all of us can see what she WROTE. And since she erred on one of the most critical terms (since the focal point of our ENTIRE debate hinges on whether or not the skin needs a certain pH range to optimally convert retinol into tretinoin), her logical conclusion and authority (on this topic) only diminish in validity and strength.

What is stranger still about the claim of retinol working best at any pH level is that it actually works best in formulas that have no pH at all (this is true of many antioxidants and cell-communicating ingredients,) such as silicone-based serums.

Again, no citation was used to substantiate this claim. While it may be true, I’d imagine that a water- and oil-based emulsion (liposomes) with chemical penetration enhancers like ethoxydiglycol, limonene, or even ethanol, while being not as stable and more drying, will be more effective than silicone-based serums due to a better delivery system.

We’ve heard the claim (as have many) that retinol can’t be combined with acidic products like AHA or vitamin C because of the pH concern, but there is no research supporting this (and we’ve looked on numerous occasions) aside from the study mentioned above, which really wasn’t talking about this issue to begin with!

As I mentioned above, the pH concern isn’t about allowing retinol to function, but allowing the skin to optimally convert it to tretinoin. When a correctly formulated hydroxy acid or L-ascorbic acid (vitamin C) product is applied to the skin, the skin is saturated with the product, and the pH (of the skin) is temporarily lowered to something close to that of the product. Glycolic acid, an alpha hydroxy acid, requires an approximate pH of <4.0 to exfoliate and penetrate the skin, while L-ascorbic acid requires a pH of <3.5. Therefore, because the pH necessary for the skin to optimally convert retinol into tretinoin is far more neutral than that, they shouldn’t be used together. Not to mention that, while pH doesn’t affect retinol all that much, it does affect hydroxy acids and vitamin-C. So if used together, the retinol won’t be optimally converted to tretinoin, and the hydroxy acid or vitamin C may not even work much at all! Talk about a “lose-lose” scenario!

Now, it’s important to note (like I said in Part I), that the pH range of 5.0-6.0 was estimated and is only required for the enzymes to convert OPTIMALLY. Since no studies have been done to compare how well the skin converts retinol to tretinoin across various pH values, right now it’s really just a “better-safe-than-sorry” attitude that I make this recommendation.

Also, keep in mind that when I say “used together” I mean like both products (retinol + acidic) are applied one after the other, with no significant wait time in between, or if they’re in the same formulation. I don’t mean that they can’t be used in the same routine. And once again, because no study has been done to see how quickly the skin homeostatically returns to its normal pH when a topical product of a different pH is applied (probably because there are too many factors that are difficult to control and can drastically alter results such as: vehicle occlusion, amount of product applied, and every individuals’ skin pH, etc…), it’s still a “better-safe-than-sorry” approach and recommendation: to apply them on different days. However, if you feel like you MUST use acid products with retinol ones at the same time, wait at least one hour between applications, just to allow for the adequate re-alignment of the skin’s natural pH, and the optimal conversion of retinol to tretinoin.

In contrast, there is research supporting concurrent use of an alpha hydroxy acid (AHA) product with retinoids. The final decision is up to you, but as long as you’re being good about wearing an SPF 15+ every day without exception, there is no research-supported legitimate reason why you can’t use your cosmetic retinol product during the daytime!

Paula uses citations #4, #5, and #6 to substantiate this claim. Studies #5 and #6 will be ignored because they both test a hydroxy acid with tretinoin… As this entire series so far has emphasized, RETINOL products need a certain pH range to allow the skin to optimally convert retinol to tretinoin!!! Of course the skin doesn’t need a pH range to convert tretinoin… it’s already TRETINOIN! Again, the fact that Paula would use citations #5 and #6 displays either a cunning attempt to fool readers (on this topic), or a serious lack of knowledge (on this topic). Both instances are quite alarming.

>>> Now study #4, as the title suggests, was done to test tolerance and acceptability, not drug interactions. So maybe they were used together, but it doesn’t tell me if retinaldehye worked better in the presence or absence of glycolic acid.

>>> Furthermore, as I can’t see the entire article (I’d have to ask a university friend to download it for me, which I can if you guys want me to), I don’t know if the two products were actually “used together” (see above for definition), or that there was a significant wait time between the two, if there were even two separate products. This is important because glycolic acid functions by thinning the top dead layer of skin. So if they weren’t “used together,” glycolic acid would naturally amplify the effects of retinaldehyde by allowing more of the latter to penetrate into the skin and penetrate more deeply, since there’s fewer layers of dead cells that the latter must first traverse.

An evaluation of the compatibility of tretinoin cream 0.05% and a glycolic acid 8% solution for acne-prone skin. Cosmetic Dermatology. 1996; 9:26–38. (#6)

Bottom Line

Ultimately, what you decide to do is your choice. My main goal is to tell you guys that in most cases, to get the best out of your routine, you shouldn’t use retinol products with acidic ones. With the right concentration and formulation (and routine of course), retinol used once per day at night time should be more than enough to satisfy most people. And if after reading through all of this, you still feel compelled to use acidic products and retinol together, please wait at least one hour between applications! Until more conclusive and specific studies are done to elucidate the various mysteries present above, this is the best that we can hope for!

I’d like to quickly point out that while I evaluated Paula’s assessment of this topic quite harshly, please keep in mind that I absolutely LOVE most of Paula’s Choice products, in addition to Paula’s own crusade to enlighten the general public with (mostly) accurate and refreshing advice. So what if I strongly disagree with a few things that she claims? It doesn’t make her any LESS awesome! But keep in mind that “everyone makes mistakes,” myself included. Besides, the WORDS being said are more important than the PERSON saying the words. Please note that, like I said in my Disclaimer, I am self-educated in the literature and am in no way a professional. But does that make my correct assessments more correct? Or my faults more wrong? No. Therefore, always seek multiple opinions on a topic, so you can make a more informed decision. And in the end, if you disagree with me, that’s perfectly fine!

What do you guys think of this article/topic/viewpoint? I’d love to hear your opinions!

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About John

The Triple Helixian is an unbiased science and research-based site that attempts to clarify and elucidate questions about skin care, while aspiring to be the most thorough and complete source of information.

Discussion

Oh my, I’m a little confused right now. Since I started using retinol at night, I moved my use of glycolic acid to the morning. In the morning I use a vitmain C serum, followed by a glycolic acid treatment. But! I don’t wait very long before applying a sunscreen. Does the application of the sunscreen change my skin’s pH and therefore deem teh glycolci useless from that point forth? I am a little confused now. I have no idea how to even include a BHA in my routine which I would like to because it keeps my pimples at bay..

No the sunscreen won’t make a huge dent in terms of efficacy of the hydroxy acid or vitamin C because there isn’t a particularly strong base present in the sunscreen to alter the pH. Definitely go ahead and apply your glycolic and then your sunscreen. Although, I would recommend that if possible, to swap out the glycolic with the salicylic acid product that you want to use, since SA provides a minor amount of additional sun protection compared to glycolic. Leave your glycolic product for the evening. 🙂

Another option is to just use your vitamin C product in the morning, followed by the sunscreen. Then use a SA and GA acid product in the evening. You can get one that’s pre-made like that, or you can mix a SA product with a GA one in a 1:1 ratio.

Thanks! I recently changed up my routine though not my products. I now use GA/SA in the evenings alternting with retinol, and vitamin C and a niacinamde complex on alternating mornings. Hopefully this works, if not I’ll probably go back to the old routine.
I have a follow up question(s) though: I realize that sunscreen isn’t particualrly basic but even if you add a neutral pH solution to an acidic one then isn’t the acidity diluted? Like when adding water to lemon juice you naturally dilute the solution because you’re reducing the parts per unit volume of the acidic molecule in the solution. I guess I’m asking about dilution and not neutralization (acid+neutral solution=higher pH vs. acid+base=water+salt). Won’t a diluted GA complex be less effective than a non-dulited one becuase the pH will go up? And depending on the volume of the netural pH substance added, couldn’t the glycolic acid be deemed largely ineffecitive? Is my logic flawed here? This thought is why I moved my acids to the evenigns so now I wait as long as I can before applying a moisturizer (which is of course water based and has a fairly neutral pH) but that’s a bit of a pain to do.. 😦

That is an excellent question, and I’m glad that you brought it up. What you’re saying is essentially accurate. However, you do need to consider the amount of the sunscreen that comes into direct contact with the acidic product. The pH of the acidic product will not change much because:

1. There simply isn’t enough contact between the two solutions to significantly alter the pH of both products. You’re layering one on top of the other, not mixing them homogeneously.

2. The substance (likely a tiny amount of some basic pH adjuster) that keeps the sunscreen in a more neutral pH range, is not present in a concentration high enough to again, significantly alter the acidic pH created by the relatively high concentration of the acidic compound.

These two points are valid due to the an acid’s “buffer zone.” It’s the small pH range surrounding an acid’s pKa, where the acid is largely resistant to pH change. Have you ever done a titration before? If you have, then you know what I’m talking about. 😉

Now obviously, it would be best to allow a good chunk of time between applications to achieve the optimal results. But who has time for that, especially during the morning rush hours? Even I only wait like 5-10 minutes because I have to go places haha. Ultimately, the difference in efficacy between waiting and not waiting a longer amount of time, may be quite small, though of course its magnitude will vary depending on the ingredients used and the person using them.

Does that make sense? I know it’s super complicated; just do the best that you can.

It’s not that retinol and acidic ingredients can’t be used together–they clearly can be as this and other studies demonstrate, it’s just that they may perform more ideally when used separately. When I mean separately, I mean to use them at different times of the day. For example, vitamin C (L-ascorbic acid only, and if it’s at a low pH; this doesn’t apply to vitamin C derivatives) during the day, and retinol during the night.

Keep in mind that studies like the one cited, only compare the use of retinol and acidic ingredients when they are used together or separately for an extended period of time, say six months. That’s not what I’m talking about. Of course someone using both ingredients for six months will have better results than someone using only one of them for six months.

What I’m talking about is a fine distinction between using the two ingredients together in the same product or layered, and using one during the morning and the other during the evening. No study has ever compared the two approaches, and it’s likely because the difference is small, maybe even negligible. But that’s just it, we don’t know.

That’s why I recommend using the two ingredients separately because you may get even better results and still have both types of ingredients in your regular routine. Not to mention that there are more effective and documented ingredient combinations than retinol and acidic ingredients. For example, vitamin C works best during the daytime with other network antioxidants to protect the skin against the sun. Their effects reinforce each other. Retinol on the other hand, is very sensitive to UV light and wouldn’t reinforced other antioxidants during the day time. In fact, the antioxidants now have to protect the retinol from photodegradation–something that can’t be completely prevented during the day time. Retinol also makes the skin slightly mores sensitive to sun exposure. I mean, why take that all that potential risk? Plus, retinol has been shown to work well niacinamide, another “must-have” ingredient that isn’t directly photoprotective (meaning it’s better used and night), and forms an inactivating complex with vitamin C (another reason why niacinamide is better used at nighttime).

It’s lots of (small) reasons like this that influence med to make this kind of recommendation. As you said, this is an old post. The research conducted and conclusions made are pretty solid (in my opinion). But it wasn’t placed within the context of all these other reasons. It’s just one reason to not use these two types of ingredients together. And I admit the way I wrote this article was overly aggressive, when in fact, it’s subject matter was just something to consider. It’s just another reason why I’m compiling the Ideal Skin Care Routine so that there will be ONE go-to place for all skin care-related concerns. Readers won’t have to try and piece everything together, and I won’t have to try and explain everything, because everything will be fitted and weaved together in the most logical sound way.

Am I making any sense? I’m definitely rambling… There’s just too much information and documentation that I need to show to really explain myself–something that like I said, will be done in the Ideal Skin Care Routine Series. But I hope this gives you a better sense of my logic.

So to summarize: it’s certainly not bad to use these two types of ingredients together as they provide excellent results. It’s just that they may work even better when used separately. However, the difference in efficacy between the two approaches may be too small or even negligible for most people. I’m simply trying to present data and some food for thought about this issue, to those who truly want to theoretically maximize their skin care routines. After all, that’s what science is about, right?

hello! i’m believe i’m fortunate to be able to use retin-a so i wouldn’t have to worry too much about the retinol metabolism. i’m more concerned about the whole pH issue. i’m assuming you have read paula’s rebuttal about the whole pH and retinol metabolism issue here: https://www.facebook.com/notes/paulas-choice/the-truth-about-using-retinol-with-aha-bha-and-vitamin-c/10151246226879004. she gave this analogy that raised a few questions for me: “Sweating also lowers the skin’s pH because of its lactic acid and other compounds, so does that mean that mean when you sweat, you have neutralized all the vitamin A in your skin? … Does this then mean you must raise your skin’s pH in order to use a retinol product?” you yourself, in order for the retinol to be converted properly, also advocated that there should be a gap of time after applying acidic products to the skin, so that the skin’s pH would return to normal. so now my question is: does hydroxy acid products stop exfoliating when the pH of the skin returns to normal? wouldnt the pH of the skin ‘neutralize’ the pH of the product and that the hydroxy acid wouldnt be able to exfoliate? i hope im making sense here =X

Yes, I’ve read all the relevant posts that she authored. I plan to address all of them, and FutureDerm’s in a series for the website The Beauty Brains. Have you heard of it? I also plan to do the same thing for the issue about alcohol in skin care.

What’s so ironic and slightly annoying is that Paula only addresses the posts made by Nicki; she doesn’t address any of the ones that I wrote. Nicki’s unfortunately are not as “correct” as I’d like them to be. Therefore, she is more open to attack because some of the facts aren’t right or not properly clarified.

Anyways, there will be a ton of commentary on both sides of the arguments included in those two series.

But to just address your question here: Let me point some of the fallacies of Paula’s argument. She uses the analogy to justify her claim that the skin does not require a pH to “process” vitamin A. Howeve, you need to keep in mind that just because an analogy makes sense, DOES NOT automatically make both comparisons correct.

For example, she always says that the skin needs multiple types of ingredients just like the body needs multiple types of foods to remain healthy. But the fact that the body needs multiple types of foods DOES NOT automatically mean her first point is correct. The analogy only works because her first point also happens to be true.

Case in point: I could argue with an analogy by saying, the lungs only need one thing: oxygen, and therefore, the skin only needs vitamin C. See? Just because the 2nd comparison is true, doesn’t automatically mean the 1st comparison is as well.

Analogies are useful to explain a complicated issue, but should NOT be used to justify the validity of the original issue. Again, it annoys me that Paula relies so heavily on them.

But anyways, if you look at the diction in the analogy that you mentioned, notice how Paula likes to use what I call “sensationalized” words like “all” “always” “never” etc.. In the relevant posts, I have not argued that an acidic pH would not allow ANY of the vitamin A to be converted. I only said that the skin has an an OPTIMAL pH range in which to transform vitamin A to tretinoin. If you take the time to look through every single post and comment where I mention this issue, you’ll notice that I have always said OPTIMAL conversion. I didn’t say a more neutral pH was absolutely necessary. And Paula can in no way say that I’m wrong, which is likely why she doesn’t address my posts. But whatever, I’ve moved way beyond that now. What matters to me is letting you guys know the truth.

Now to answer your question: Hydroxy acids (HAs) actually do stop exfoliating your skin when the pH returns to normal! But you have not think of the pH of your skin as a constant number. The pH of the skin fluctuates over time. For example, when you wash your face with regular soap, it’ll become more alkaline. When you use ana hydroxy acid, it will become more acidic. Why do you think HA products have to have a certain pH in order to function? It’s to maintain a pH low enough for the acid to exfoliate. Because over time, the skin will swing back to its “regular” pH, which will vary from person to person. If the pH of your skin didn’t change, then if you applied HAs to your face, they’d keep exfoliating until you had none left! And that’s obviously not the case.

ah i see. come to think of it, i myself, as a language student didn’t even realize that! oh well, 2nd year writing, here i come. as usual, thanks so much for going all out to explain everything. keep up the hard work and continue to democratize derm knowledge for your readers! =D thanks agaiN!

Hi John,
Rereading this article I need to clarify a few points which affect my skincare routine in regard to retinods.

I has been my understanding that it takes 30-45 minutes for the conversion of retinol to tretinoin, please correct if wrong.
I need to understand first the time period of likely effect from a single application – (both OTC retinol and Nicki’s time release retinol would be helpful)

In the study you refer to involving retinol and daytime use with sunscreen, the word ‘degradation’ has me a bit confused
Does the ‘degradation’ affect potency or does the word as used here refer to chemical changes with the potential to damage the skin. i.e., is this a loss of effect issue or a potentially negative effect issue?
Also, if the conversion of retinol to tretinoin takes less than an hour, what is it that ‘degrades’ over the period of 4 hours?

Clearly I’m missing something, can you fill in some blanks for me please?

Hm, I never said that it takes 30-45 minutes for the complete conversion of retinol to tretinoin; there isn’t a established general number out there for that measurement. The only reason why I recommended for a 30-45 minute wait time between applications is so that the skin has a chance to return to a more neutral pH value, since the application of the acid temporarily lowers the pH of the skin.

Again however, I’m not saying that the pH of the skin WILL return to “normal” after that length of time. It’s just an best guess estimation. There is no study that elucidates how long it takes skin to return to its regular pH. I’m also sure that this theoretical value can also drastically vary depending on product, person, and amount of product.

Does that make sense?

As for the word “degradation,” what I was referring to was the breaking down of the retinol molecule itself, since it is very sensitive to sunlight. Therefore, if it’s broken down, it can’t be metabolized into tretinoin.

So quick recap:

1. It is unknown how long it takes the skin to convert retinol into tretinoin, keeping in mind that the ratio converted is somewhere between 5-10%.

2. There is no established time frame as to how long it takes the pH of the skin to return to its normal value.

3. Sunlight “degrades” retinol by breaking it down/apart; the byproducts are not recognized by the skin’s enzymes. They will therefore not be able to convert retinol to tretinoin.

4. Ultimately, because there are quite a few unknowns, it’s just more reliable to simply wait 30-45 minutes between applications, keeping in mind that this time frame is simply a best guess estimation.

Hi John, your parts I & II on Retinoids, Tretinoin etchave been valuable thank you.
I have used tretinoin for almost 30 years and have skin much younger than most at 56yrs. I am currently using a Retinol product to avoid the irritation from Tretinoin which I’ve always managed previously but which worsened when I added a Vit C,E, niacinamide & ferulic acid product, a BHA product, various antiglycation ingredients and palmitoyl TetraPeptide, Palmitoyl Oligopeptide to the regimen
The switch to Retinol from Tretinoin has helped with irritation but I am concerned about a quote from a post by you on Futurederm (below)

Can you explain why retinol can never fully replace Tretinoin please?

‘ To make a blanket statement that retinol will do the same thing as tretinoin, with just more time, is lazy, inaccurate, . This topic will be explored further in Part III, which will explain why retinol can never replace Tretinoin’

Thank you John, I need to understand this from you so I can further refine my product choices and skincare routine.

First of all, relax! Your routine looks pretty good, though I’m a little concerned about some negative interactions between the many ingredients that you use. I’m sure your skin looks fantastic! But anyways, like I said, I will be writing all about this idea that retinol can never replace tretinoin in Part III.

I actually was going to write this post today, but something came up and I didn’t have the time. 😦 I hope to write this tomorrow.

But a quick note: as long as you haven’t had a lot of sun exposure, the above-mentioned statement may not meaningfully apply to you. It depends on a variety of factors.

And with that in mind, stay tuned! I really, REALLY hope to get this out tomorrow.

And while I am no doctor myself, I don’t think you should have any problems with ferulic acid in skin care. As I’m sure you know, celiac disease is caused by an inflammatory reaction to gliadin, a gluten protein found in wheat, barley, and rye amongst others. And while ferulic acid can be derived from these, that doesn’t mean that it will trigger a reaction, especially when applied to the skin. Not to mention that its structure and function doesn’t even resemble gliadin.

Furthermore, most if any of the ferulic acid content that penetrates past the numerous layers of the skin and is absorbed into the bloodstream, will be conjugated into sulfates and glucuronides and excreted via urine. I explained this process in part III of my sunscreen series on toxicity. And that process doesn’t go anywhere near your small intestines.

That’s just my assessment and I haven’t found any other research indicating otherwise. Perhaps you may want to ask the other blogger what her source is for that warning.

Thanks John, I might contact her because that comment (hers) really surprised me. I was diagnosed over 10 years ago, so am pretty in tune with what to do and what not to do – worrying about skin care ingredients isn’t something that has been on my radar. I have definitely had allergic reactions to things, but not in the same way that I react to food.

I am going to check it out further, but as usual, a very thorough and logical answer!!

I have another question (or two). One is, since I will no longer use a retinol product during the day, what is a good treatment cream/serum to use instead – apart from one of the CE Ferulic options? Currently I am using the Resist toner and then just a tinted moisturiser on top. I need additional sunscreen obviously, but is there anything else that should go in between?

The second is about PH and what goes together. I have just reordered the weekly resurfacing treatment and I definitely need to put something on top of it for moisture. As I tend to put it on just before bed, I need to use something that can go on top within a few minutes rather than waiting for half an hour. Do you have any suggestions?

For the day routine, just use something lightweight and contains antioxidants to boost your UV protection. You don’t want too many layers, so yeah. The CE Ferulic option is an excellent one, but it’s not the only one. I recommend it just because that specific formulation has quite a lot of research behind it, but theoretically anything with high amounts of different antioxidants will boost the level of protection. Look for ingredients that have at least moderate amounts of studies confirming antioxidant and photoprotective abilities like green tea, pomegranate, and resveratrol, amongst others.

As for the pH issue, I really recommend waiting a while, because then your options will be much varied and wide in range! But if you insist on applying your moisturizer immediately afterwards… there are still a few options:

One, you can apply something on top that has a similar pH to the weekly treatment, and most moisturizers with a low pH are exfoliants in themselves. So you’ll want something that’s quite weak in potency, just so your skin isn’t irritated. Something like the Proactiv Clarifying Night Cream would be good. It only contains 1% salicylic acid, while being contained in a nice lotion-cream that’s appropriate for normal to dry skin types. It also includes some antioxidants, and a bit of retinol. While the retinol will be less “optimally” converted with the low pH, you don’t use retinol anyways. So that’s fine. Another very affordable option would be the Neutrogena Oil-Free Acne Stress Control 3-In-1 Hydrating Acne Treatment. While that sounds scary, with 2% SA, it’s really quite gentle, due to the inclusion of several anti-inflammatories such as green tea. But I’m not sure if this will provide enough moisture: it’s in a silky silicone and water emulsion that’s very lightweight, and good for those with combination oily to oily skin types. You may have to experiment to see which works better.

Two, you can apply something on top that doesn’t have a pH; so something that contains 0% water. Something like a silicone-enriched serum would work, such as the Paula’s Choice RESIST Super Antioxidant serum. And since you were already considering that, perhaps this will be a good option for you.

Three, you can completely remove the Weekly treatment routine and replace it with something similar, but contains more emollients, humectants and/or occlusives to boost moisturization. Something like the Olay Regenerist Night Resurfacing Elixir would be a good choice. It contains 8-10% glycolic acid like the Weekly Treatment, while containing some green tea and grape seed extract. It may or may not be moisturizing enough for you; it has a lightweight glycerin-based texture that’s appropriate for normal to combination oily skin types.

It works well all retinoids, with the exception of retinol and retinaldehyde of course. It’s the whole optimal conversion pH thing again lol, since azelaic acid has an acid pKa, etc… But with any prescription retinoid, I’ve been shown to work in combination in fight acne, inflammation, melasma, and many others. I really wish AZ acid was available OTC because it’s quite a multi-purpose ingredient! Ack! If only.

Fascinating! Unfortunately, interpretation of scientific literature really is in the eye of the beholder, and science is often more art, or marketing, than science. I appreciate all of your research and attention to detail. I too have a lot of respect for Paula Begoun, and I will continue to buy Paula’s Choice products. However, I find some of the claims PC has made, mostly about the RESIST line, pretty far-reaching. Ironically, Paula’s books have taught me to be skeptical of such claims. I started buying PC products forever ago. I don’t remember any of the claims or marketing seeming far-reaching until the RESIST line. In some ways, I expect more honesty or transparency, but I guess PC is competing on a larger scale now. Overall PC is still a great company, but your article reminds me of the importance of using multiple sources for research.

You’re certainly a good source! Paula is too. But since she’s selling something, I’m naturally skeptical. I appreciate all of your time and research. It must have taken you hours on PubMed. Now the whole retinol issue is much less murky for me. It’s been easier just to buy various forms of Retin-A.

What a helpful post! Although the main topic reiterated most of what i alredy knew, there were still some helpful tidbits to pick up.
But now you have created a whole new dilemna for me! I have been using the CE Ferulic serum in the a.m. (15% L-ascorbic acid, etc) followed by the Nia 24 barrier repair cream 15 minutes later (5 Nicotonic acid – sp?) solely because i thought you couldn’t use retin-A with an acidic product……help! I so want to have that niacinimide in my routine, but figured that peptides would be better over the retin-a (Tazorac .05% – is this the same as tretinoin?).
Which is the optimal combination………..?ugh.

You should be fine with using the Nia with the CE Ferulic serum. While niacinamide (a more stable version of nicotinic acid) has been shown to slightly degrade L-ascrobic acid, the vitamin C is being stabilized by the vitamin E and ferulic acid. That’ll be fine!

Most peptides that I’ve encountered don’t have too much in vivo documentation, but yeah they should work fine over the Tazorac. And no, Tazorac (chemical name: tazarotene) is not the same as tretinoin. However, that shouldn’t matter in this situation, since this post is talking about retinol. The skin needs a certain pH to optimally convert retinol to tretinoin. On the other hand, the skin doesn’t need that certain pH to optimally convert tretinoin, since it’s already tretinoin!

So your current routine of morning: Vitamin CE, Nia24; followed by evening: Tazorac, peptides, is perfectly fine! I hope that allayed some of your doubts! 🙂

Why thank you, nice to be back. I have been following you avidly still, just not commenting for some strange reason – oh yeah, I tend towards introversion :-).

I edited my earlier post and obviously didn’t proofread – doh.

I meant Retinol disaster averted as the Vit C and the retinol wouldn’t mix, so better to eliminate the Retinol before starting the Vit C. Definitely getting the vit c, although now am confused about the sunscreen (based on your sunscreen post). This whole nano particle thing…I am also not sold on the CE Ferulic, it seems like an awful lot of money for a potentially unstable product. Is the PC serum (the one that is recommended to use as a primer, the name escapes me for the moment) sufficient Vit C wise or should I try the Timeless? Ah yes, slightly hooked on FutureDerm (that is your fault young John).

Anyway, I was using the daily smoothing in the morning and alternating the serum and the MB – not the same night. My point was whether the daily smoothing and the serum together was overkill – I am almost out of the serum, so maybe just not bother to re purchase as there is no way I would remember to put something on half an hour later. I also have the weekly resurfacing one, well I am out of that actually but really want it again as I found it to be really good, whereas the serum – not sure.

See, I have all this stuff and, and, and…Not sure what is best, although it is fun to experiment. My skin is definitely better BTW, but really keen to add Vit C to the mix.

Oh okay, that’s what I thought you meant about the vitamin C and retinol issue.

The vitamin C form in the PC RESIST Super Concentrate (if that’s what you’re talking about) is actually lipid-soluble, and because the product doesn’t have water, it has no PH. It can be used with the retinol serum. Though I can’t imagine why you’d want to use both since they aren’t exactly lightweight. But in this article, the vitamin C that I’m referring to is L-ascrobic acid only (since it requires a pH of <3.5 to function. It does not apply to any vitamin C derivatives; particularly the lipid-soluble ones.

And you can try the Timeless serum, but FutureDerm is actually coming out with it's own CE Ferulic acid product next month! I'm assuming that it'll be more expensive (based on how their retinol serum is priced), perhaps the Timeless might be a better buy. I for one, am very excited that FutureDerm is coming out with their version, since I'd NEVER shell out the money for the Skinceuticals version.

Also, if the retinol serum (after an entire bottle) isn't doing you much good, then perhaps your skin just isn't very responsive to that particular formulation. But keep in mind that it does contain "good" amounts of vitamin C and E as well, just like the Super Concentrate Serum. So I don't know if you'll notice a bigger difference with the Super C. Granted it does contain a lot of other good ingredients, but the choice is yours of course! Or you could try the FutureDerm retion serum. It's still at the introductory price. And I'm not pushing that product just because I'm affiliated with them. It's just another option. I'll actually be coming out with my independent product review and an interview with Nicki about the retinol serum later this week or next week!

I am tempted by the FutureDerm Retinol, but the shipping is $25! Maybe I will wait until they bring out the Vit C and buy them together to justify it. So many of the products that are recommended (like the NIA) we just can’t get here or Amazon won’t deliver to Australia.

It is hard to know what is and isn’t working with the skin care stuff I am using. I have seen overall improvement but there is always room for more. I am not getting that OMG this stuff is awesome feeling although I did feel a major difference in the morning when I used the weekly resurfacing treatment. However, that isn’t Retinol so not terribly relevant to the topic at hand really.

Oh dang! I completely forgot that international users are charged that crazy shipping fee. 😦 BOO.

And it is hard to know what works and what doesn’t work. Most things in skin care are about maintenance and preventative care, rather than treatment. 😦 But I’m glad to hear that you’re loving the RESIST weekly treatment!

Hi John,
Gee, it is almost a case of the more you know, the more confusing it gets. I do thank you though as I think this article has saved me from a potential skin drama with summer on the way.
I bought some of the ‘Resist’ line products a few months ago, and for some reason thought the daily retinol treatment one was for daytime use.

I was just about to buy the serum with Vitamin C to wear under sunscreen, so potential no no averted. It is confusing to know what to use and when though. I have the daily smoothing and the retinol serum and the Moisture Boost Hydrating cream, it does seem a bit much to use them all at night. Maybe it should be Paula’s (too much) Choice.

I’m glad that you’re liking PC products. But let me ask you a few questions:

1. Why is the vitamin C serum a no-no for wearing under sunscreen? Because that’s sounds perfectly great to me.
2. Why do you use both the retinol serum and the Moisture Boost Cream? If I remember correctly, the retinol serum is quite emollient. I don’t think both are necessary. Or at least just apply the MB to the driest areas.

Also note, as I said in this article, you shouldn’t use hydroxy acids with retinol, so don’t use the daily smoothing and retinol serums together; unless you wait like 30-60 minutes between applications.

Damn blogger reading list, I was finding it awkward that you haven’t post anything in a while, turns out you did and blogger didn’t show it -_-”

This is very interesting, my current doubt is about salicylic acid, just bought a cream with 2% and don’t know when to use it.
In my current routine I use vitamin C & hyaluronic acid in the morning and niacinamide at night plus retin-A 2 or 3 times a week also at night. Can salicylic acid be used with vitamin C? or with niacinamide? or with both?

I have already read some stuff on the subject, but found it confusing, as ones said that niacinamide shouldn’t be used with salicylic acid others that it was OK, vitamin C there is a lot of stuff on vitamin C + “acids” but I didn’t find it very specific and got the feeling they were referring to retinoids rather than AHA and BHA.

P.S.: please excuse me if you have already wrote on that matter, I am a little behind on your latest posts.

Yeah salicylic acid can be used with vitamin C, as long as the vitamin C is the water-soluble L-ascrobic acid. I personally don’t think niacinamide should be used together with L-ascrobic acid (especially during the day), because the former tends to degrade the latter in conjunction with UV irradiation. Here’s a link for that claim: http://www.ncbi.nlm.nih.gov/pubmed/22014159

I tend to group hydroxy acids with L-ascrobic acid, and niacinamide with things like retinol, green tea, etc..

Thank you 🙂
Guess I’m doing it right then. Yes it did, I’ll use it in the morning before Vitamin C 🙂

I was thinking about using something with glycolic acid in the nights I don’t use retin-A, but from what you wrote it wouldn’t be a nice match with niacinamide, maybe I get something with green tea instead.

Well now, the study only said that niacinamide slightly degraded L-ascrobic acid, but the abstract didn’t say that it was because of the pH. I can find out the reason if you’d like me to.

But yeah, the reasoning that niacinamide won’t work with glycolic acid because of incompatible pH values, isn’t valid. I’m pretty sure that you can use them together. But better yet, use a glycolic acid product, and then use something with BOTH niacinamide and green tea together! You’ll get even MORE out of your routine that way.

Thanks, not confusing at all, my academic studies are in the art field so since the last time I studied science was in 9th grade I sometimes have difficulty understanding some concepts right away, but I do like to know and to learn, and you do explain it very well, which is why I like your blog.

I’ll sure be adding those to my routine once my skin adapts to the salicylic acid 🙂

Yes it still will because NA is known for form a 1:1 complex with AH2!UV irradiation will increase the rate of degradation, in addition to generating photosensitizing by-products that are pro-oxidant. Here’s a citation for that:

Great post!
Does this apply to tretinoin as well? Many dermatologists say that tretinoin should be the first think you apply to your skin and it’s best to not apply anything else, so would an acid (AHA or BHA) or a vitamin C serum get in the way of tretinoin as it would with retinol?

No this particular pH concern doesn’t apply to tretinoin because tretinoin doesn’t need to be converted. It’s already tretinoin. 🙂 When derms say to apply it first to the skin, it’s just so that the tretinoin can work without interference. If you apply anything under it, it’ll just to act as a buffer, due to the high irritation potential of tretinoin. So with a buffer, tretinoin will basically be less irritating, but also be less effective, since less of it will penetrate into the skin.